Diagnostic Superiority of Transperineal Combined Fusion Biopsy Versus Transrectal Ultrasound-Guided Biopsy: Lower Upgrading Rates and Better Concordance with Post-Surgical Histopathology

<b>Background/Objectives:</b> Accurate histopathological grading of prostate cancer at the time of biopsy is essential for guiding treatment decisions and minimizing the risks of both overtreatment and undertreatment. A key challenge in prostate cancer diagnostics is the phenomenon of upgrading, wherein the cancer appears more aggressive in the radical prostatectomy specimen than initially indicated by biopsy. Such discrepancies can compromise therapeutic planning. This study investigates whether transperineal combined fusion biopsy (ComBx), incorporating MRI-targeted and systematic sampling, achieves greater concordance with final prostatectomy histopathology compared to conventional transrectal ultrasound-guided systematic biopsy (TRUS-Bx). <b>Methods:</b> This retrospective cohort study analyzed 500 men aged 46 to 79 years (mean age 65) who underwent prostate biopsies between 2017 and 2022 at a single tertiary institution. Patients were stratified into two groups: 250 underwent TRUS-Bx using a 12-core systematic approach, and 250 underwent ComBx guided by software-based MRI-ultrasound fusion targeting PI-RADS ≥ 3 lesions, followed by systematic sampling. Histopathological grading from biopsies was compared with final pathology following radical prostatectomy. Concordance, upgrading, and downgrading rates were analyzed using appropriate statistical methods. <b>Results:</b> Prostate cancer was diagnosed in 113 patients in the TRUS-Bx group and 152 in the ComBx group. Among these, 89 TRUS-Bx and 68 ComBx patients underwent radical prostatectomy at our center. Histological upgrading occurred statistically significantly more often in the TRUS-Bx group (35%) compared to the ComBx group (16%) (<i>p</i> = 0.004). Concordance between biopsy and prostatectomy grading was statistically significantly higher in the ComBx group (63%) than in the TRUS-Bx group (49%) (<i>p</i> = 0.042). No significant difference in downgrading rates was observed between groups. <b>Conclusions:</b> Transperineal combined fusion biopsy substantially improves concordance with final prostatectomy histology and significantly reduces the risk of upgrading compared to transrectal systematic biopsy. These findings support the adoption of ComBx as a more reliable diagnostic strategy for accurate grading of clinically significant prostate cancer, with implications for improving treatment precision and patient outcomes.